Method and system for noninvasive detection of fetus chromosome aneuploid

A technology for aneuploidy and chromosomes, applied in the field of medical testing, can solve problems such as not considering the sequence preference between chromosomes, affecting the accuracy of final results, and constructing an optimization model for sex chromosome data

A technology for aneuploidy and chromosomes, applied in the field of medical testing, can solve problems such as not considering the sequence preference between chromosomes, affecting the accuracy of final results, and constructing an optimization model for sex chromosome data

CN103525939AActive Publication Date: 2014-01-22BOAO BIOLOGICAL CO LTD
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  • Method and system for noninvasive detection of fetus chromosome aneuploid
  • Method and system for noninvasive detection of fetus chromosome aneuploid
  • Method and system for noninvasive detection of fetus chromosome aneuploid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Example 1: Building a reference database

[0095] 1. Select control blood samples

[0096] 500 peripheral blood samples from pregnant women whose gestational weeks were greater than or equal to 12 weeks and had no chromosomal abnormalities in karyotype analysis were selected to form the control blood samples in the reference database A (Reference A). Among them, the blood samples of 200 pregnant women with normal female fetuses constitute the control blood samples in the reference database B (Reference B).

[0097] 2. Accurate positioning of sequencing data

[0098] Compare the sequencing data with the human genome standard sequence hg19 to determine the exact position of the base sequence on the chromosome.

[0099] 3. Quality control of sequencing data

[0100] In order to ensure the quality of the sequencing results and avoid the interference of some repetitive sequences, low-quality sequences were eliminated, and the bases located in the tandem repeat and transpo...

Embodiment 2

[0107] Example 2: Construction of determination parameters and threshold ranges for X chromosome aneuploidy in male fetuses

[0108] 1. Calculate the Z value of X and Y chromosomes in male fetuses

[0109] Using Reference B as a reference database, calculate the Z values ​​of fetal X and Y chromosomes in the blood samples of pregnant women carrying normal male fetuses according to formula 1, that is, Z X and Z Y .

[0110] Z i =(x i -μ i ) / σ i (Formula 1)

[0111] i: chromosome number;

[0112] x i : Unique base percentage of chromosome i in the analysis data;

[0113] mu i : The average value of the Unique base percentage of chromosome i in the reference database;

[0114] b i : The standard error of the Unique base percentage of chromosome i in the reference database.

[0115] 2. Construct Z in male fetus X and Z Y relationship model between

[0116] According to the calculation formula of Z value, Z X and Z Y Both are related to the concentration of fe...

Embodiment 3

[0126] Embodiment 3: detection of the blood sample to be tested

[0127] 1. Whole genome sequencing of blood samples to be tested

[0128] Seven pregnant volunteers participated in this test, and the blood samples were numbered N1-N7. The results of karyotype analysis showed: 1 fetus with trisomy 21, 1 fetus with trisomy 13, 1 fetus with trisomy 18, and 1 male fetus with an extra Y chromosome , 1 pregnant with a female fetus lacking one X chromosome, 1 pregnant with a normal female fetus, and 1 pregnant with a normal male fetus.

[0129] The peripheral blood of each pregnant woman is drawn, centrifuged to obtain plasma, and then DNA is extracted from the plasma, using the Ion Proton of Life Company TM Sequencers perform large-scale, high-throughput sequencing. The above blood samples were collected by Guangzhou Women and Children's Medical Center.

[0130] 2. Count the percentage of Unique bases in chromosomes in the blood sample to be tested

[0131] By comparing and fil...

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Abstract

The invention belongs to the medical detection field, and discloses a method and a system for noninvasive detection of fetus chromosome aneuploid. The disclosed detection method and system also relate to a method and a system for elimination of sequencing GC preference in chromosomes and among chromosomes and a method and a system used for the relation model of the Z values of X and Y chromosomes in a normal male fetus. Through elimination of influences of sequencing GC preference in chromosomes and among chromosomes, the relation model of the Z values of X and Y chromosomes in a normal male fetus is built, and the determination threshold of difference between the theoretical value and the actual value of the Z value of the X chromosome is built. The accurate detection of fetus chromosome aneuploid, especially sex chromosome aneuploid is achieved.

Description

technical field [0001] The invention relates to the field of medical detection, in particular to a method for non-invasive detection of fetal chromosomal aneuploidy and a system for non-invasive detection of fetal chromosomal aneuploidy. Background technique [0002] Chromosomal aneuploidy is the most common chromosomal abnormality in fetuses, which can be divided into autosomal aneuploidy and sex chromosome aneuploidy according to different chromosome types. Autosomal aneuploidy mainly includes trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome), among which trisomy 21 is the most common , the incidence rate is about 1 / 800. Sex chromosome aneuploidy mainly includes Klinefelter syndrome (47, XXY), XYY syndrome, Turner syndrome (45, X) and superfemale syndrome (47, XXX), and the male incidence is about 1 / 500 , the female incidence rate is about 1 / 850. Prenatal diagnosis of fetal chromosomal aneuploidy is an important means to reduce bi...

Claims

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Application Information

Patent Timeline
22 Jan 2014
Publication
CN103525939A
IPC
C12Q1/68; G06F19/20
CPC
C12Q1/6881
Inventors
糜庆丰; 彭春芳